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Cited by 182Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Evaluation of α-synuclein immunohistochemical methods used by invited experts

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Beach, Thomas G., White, Charles L., Hamilton, Ronald L., Duda, John E., Iwatsubo, Takeshi, Dickson, Dennis W., Leverenz, James B., Roncaroli, Federico +5 more·2008·Acta Neuropathologica
DOI 10.1007/s00401-008-0409-8PMC PMC2708176
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Abstract

The use of alpha-synuclein immunohistochemistry has altered our concepts of the cellular pathology, anatomical distribution and prevalence of Lewy body disorders. However, the diversity of methodology between laboratories has led to some inconsistencies in the literature. Adoption of uniformly sensitive methods may resolve some of these differences. Eight different immunohistochemical methods for demonstrating alpha-synuclein pathology, developed in eight separate expert laboratories, were evaluated for their sensitivity for neuronal elements affected by human Lewy body disorders. Identical test sets of formalin-fixed, paraffin-embedded sections from subjects diagnosed neuropathologically with or without Lewy body disorders were stained with the eight methods and graded by three observers for specific and nonspecific staining. The methods did not differ significantly in terms of Lewy body counts, but varied considerably in their ability to reveal neuropil elements such as fibers and dots. One method was clearly superior for revealing these neuropil elements and the critical factor contributing to its high sensitivity was considered to be its use of proteinase K as an epitope retrieval method. Some methods, however, achieved relatively high sensitivities with optimized formic acid protocols combined with a hydrolytic step. One method was developed that allows high sensitivity with commercially available reagents.

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  • Greater sensitivity for detecting Lewy bodies can be achieved with immunohistochemistry for α-synuclein compared to H&E.

    “LBs may be detected in neurons of medulla, pons and midbrain with hematoxylin and eosin (H&E)-stained sections; however, greater sensitivity can be achieved with immunohistochemistry for α-synuclein and this approach is strongly preferred [3,4,13].”

    From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [13]

    The Introduction (page unavailable) calls α-synuclein immunohistochemistry the method of choice for diagnosing Lewy body disorders, supporting its preferred use. The paper compares immunohistochemical methods with one another, however, and does not establish that they detect Lewy bodies more sensitively than H&E staining. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Neocortical LBD is correlated with greater likelihood of cognitive impairment.

    “For cases with incomplete clinical history, we note that “Neocortical LBD” is correlated with greater likelihood of cognitive impairment [1,11-13,22,31-33,38,46,49,52].”

    From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [13]

    The Methods (Human subjects; page unavailable) say the selected cases had varying synuclein pathology and diagnoses, but the study used them to assess staining-method sensitivity. The Discussion (page unavailable) addresses detection and grading of pathology, not whether neocortical Lewy body disease correlates with cognitive impairment. Searches for neocortical disease, cognitive impairment, dementia, and clinical correlation found no passage establishing the claimed relationship. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Beach, T. G., White, C. L., Hamilton, R. L., Duda, J. E., Iwatsubo, T., Dickson, D. W., Leverenz, J. B., Roncaroli, F., Buttini, M., Hladik, C. L., Sue, L. I., Noorigian, J. V., & Adler, C. H.
Affiliations
  • Banner Sun Health Research Institute (US)
  • The University of Texas Southwestern Medical Center (US)
  • University of Pittsburgh (US)
  • Philadelphia VA Medical Center (US)
  • The University of Tokyo (JP)
  • Mayo Clinic (US)
  • University of Washington (US)
  • Imperial College London (GB)
  • Elan Pharmaceuticals, Inc. (Ireland) (IE)
Corresponding author
Beach, Thomas G.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2008-07-15
Volume
116
Issue
3
Pages
277-288
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-008-0409-8
PMC
PMC2708176
OpenAlex
W2084366703
Cited by
182
References
51
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 5 · 2022: 12 · 2021: 10 · 2020: 11 · 2019: 17 · 2018: 14 · 2017: 8 · 2016: 14 · 2015: 13 · 2014: 10 · 2013: 11 · 2012: 9
FWCI
5.99
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (P30-AG-19610, P50AG005133, P30AG019610, P50AG005136)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
alpha-synuclein, immunohistochemistry, Lewy body disease, diagnostic sensitivity, proteinase K, formic acid, Lewy bodies, Parkinson's disease, method comparison
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Formaldehyde, Humans, Immunohistochemistry, Pathology, Clinical, Sensitivity and Specificity, Staining and Labeling, Reproducibility of Results, Paraffin Embedding, Tissue Fixation, Lewy Body Disease, alpha-Synuclein

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